key: cord-0781342-4bhhmrpa
authors: nan
title: World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO 2021): Oral Communication Abstracts
date: 2022-02-16
journal: Osteoporos Int
DOI: 10.1007/s00198-021-06112-0
sha: 1d13dc86051dd137a5efa02ea845c1b285458a2a
doc_id: 781342
cord_uid: 4bhhmrpa

nan

Objectives: To assess the associations between disease modifying antirheumatic drugs (DMARDs) and incident as well as progression of radiographic distal interphalangeal (DIP) osteoarthritis (OA) in rheumatoid arthritis (RA) patients. Methods: We performed two observational cohort studies in the Swiss Clinical Quality Management registry (SCQM) [1997] [1998] [1999] [2000] [2001] [2002] [2003] [2004] [2005] [2006] [2007] [2008] [2009] [2010] [2011] [2012] [2013] [2014] . RA patients who had ≥ 2 eligible hand radiographs were included at their first eligible radiograph (i.e. if all 8 DIP joints could be scored).

Modified Kellgren-Lawrence scores (KLS) were used to define incident/existing DIP OA (i.e. KLS ≥ 2 in ≥ 1 DIP joint), and progression of existing DIP OA (i.e. increase of ≥ 1 in KLS in ≥ 1 DIP joint). We divided the study population into two cohorts based on whether DIP OA was present or absent at cohort entry (cohorts 1 and 2, respectively). Cox time-varying regression were performed to estimate hazard ratios (HR) with 95% confidence intervals (CI) of DIP OA progression (cohort 1) or incidence (cohort 2) in the mutually exclusive exposure groups biologic (b) DMARD monotherapy, bDMARD/ conventional synthetic (cs) DMARD combination therapy, past DMARD use, or no DMARD use, when compared to csDMARD use. Results: Among 2234 RA patients with 5928 eligible radiographs followed for an average of 3 years, 1340 patients had radiographic DIP OA at cohort entry (cohort 1). bDMARD monotherapy had an increased risk of radiographic DIP OA progression compared to csD-MARD monotherapy (adjusted HR 1.36, 95% CI 1.08-1.71). The risk was not significant in csDMARD/bDMARD combination users (HR 1.13, 95% CI 0.97-1.32), absent in past DMARD users (HR 0.99, 95% CI 0.68-1.43), and significantly lower among non-DMARD users (HR 0.56, 95% CI 0.34-0.93). In 894 patients without initial DIP OA (cohort 2), the risk of incident OA did not differ between treatment groups. Conclusions: Our results suggest that monotherapy with bDMARDs is not associated with incident DIP OA but may increase the risk of radiographic progression of existing DIP OA when compared to csDMARDs.

Results from the FRAME and extension study (NCT01575834) of romosozumab (Romo) for the treatment of postmenopausal (PM) osteoporosis (OP) showed significant reductions in vertebral (V) and clinical fracture (fx). 1 This post hoc analysis assessed efficacy and safety of Romo vs placebo (PBO) in women enrolled in Europe (EU). Materials and Methods: PM women with OP at the hip were randomised 1:1 to Romo 210 mg or PBO monthly to Month (M) 12, followed by denosumab (Dmab) 60 mg every 6 months to M36 in both groups. We assessed least squares mean % change from baseline (CfB) in bone mineral density (BMD) at lumbar spine (LS), total hip (TH) and femoral neck (FN); fx outcomes and adverse events (AEs). Vfxs were assessed by baseline and yearly X-rays and analysed by logistic regression; other fx types were captured at time of event and analysed by Cox proportional hazards model. Results: 3013/7180 patients (pts) (42%) were enrolled in EU (1494 Romo; 1519 PBO). Incidence of all fx types was lower for Romo vs PBO at M12 and Romo → Dmab vs PBO → Dmab at M36 (Table) . Similar reductions were observed at M24. BMD CfB were greater for Romo vs PBO pts at M12 and Romo → Dmab vs PBO → Dmab at M36 for LS (M12/M36 differences: 12.3%/10.1%), TH (5.2%/4.6%) and FN (5.0%/4.5%) (all p < 0.001). Incidence of AEs and serious cardiovascular events were balanced between groups throughout. Conclusion(s): In EU pts, Romo treatment resulted in early and sustained risk reduction for all major fx types.

References: 1. Cosman F. NEJM 2016;375:1532-43 Acknowledgements: Funded by UCB Pharma and Amgen Inc. Medical writing by Costello Medical. Disclosures: AFP: Research grants (to institution) Amgen, Roche; Consultancy/Lecture/advisory board fees: Amgen, Alexion, Amgen, Eli Lilly, Fresenius, Gedeon-Richter, Genericon, Ipsen, Ratiopharm, Roche, Sandoz, Sanofi-Aventis, Shire-Takeda, Stada and UCB Pharma; BL: Research grants (to institution): Amgen and Novo Nordisk; Advisory boards and lectures: Amgen, Eli Lilly, Gedeon-Richter, Gilead and UCB Pharma; CL: Employee of UCB Pharma; EC: Grants from Amgen; EG: Consultancy fees, lecture fees and/or travel fees from Alexion, Amgen, Sandoz, Takeda and UCB Pharma; EJG: Consultancy and/or speaker and/or Investigator for Amgen, Asofarma, Astellas, AstraZeneca, Boehringer, BMS, FAES, Helios-Fresenius, Italfarmaco, Janssen, Lilly, MSD, Mundipharma, Novo Nordisk, Sanofi, Shire, Technopharma, UCB Pharma and Viatris; JT: Employee of UCB Pharma; MO: Employee of Amgen; PL: Grants and/or advisor from Amgen, UCB Pharma, Richter and Teva; ZW: Employee of Amgen and owns stock in Amgen.

N. Veronese 1 , L. Smith 2 , E. Zigoura 3 , M. Barbagallo 1 , L. Dominguez 1 , C. Cooper 4 , R. Rizzoli 5 , J.-Y. Reginster 6 , S. Maggi 7 , A. Pilotto 3 1 university of Palermo, Palermo, Italy, 2 Anglia Ruskin University, Cambridge, United Kingdom, 3 Galliera Ente Ospedaliero, Genova, Italy, 4 University of Southampton, Southampton, United Kingdom, 5 University of Geneva, Geneva, Switzerland, 6 University of Liège, Liège, Belgium, 7 Consiglio Nazionale delle Ricerche, Padova, Italy Background: Fractures increase risk for disability and poor quality of life in older people. Frailty may be associated with higher fracture risk, but limited research has been carried out using a multidimensional approach to frailty assessment and diagnosis. The present research aimed to investigate whether the multidimensional prognostic index (MPI), based on comprehensive geriatric assessment (CGA), is associated with the risk of fractures in the Osteoarthritis Initiative (OAI) study. Methods: Community-dwellers affected by knee OA or at high risk for this condition were followed-up for 8 years. A standardized CGA including information on functional, nutritional, mood, comorbidities, medications, quality of life and co-habitation status was used to calculate the MPI. Fractures were diagnosed using self-reported information. Cox's regression analysis was carried out and results are reported as hazard ratios (HRs), with their 95% confidence intervals (CIs), adjusted for potential confounders. Results: The sample consisted of 4,024 individuals (mean age 61.0 years, females = 59.0%). People with incident fractures had a significant higher MPI baseline value than those without (0.42 ± 0.18 vs. 0.40 ± 0.17). After adjusting for eight potential confounders, people with an MPI over 0.66 (HR = 1.71; 95%CI: 1.29-2.28) experienced a higher risk of fractures. An increase in 0.10 point in MPI score corresponded to an increase in fracture risk of 6% (HR = 1.06; 95%CI: 1.01-1.11). Higher MPI values were also associated with a higher risk of non-vertebral clinical fractures. Conclusion: Higher MPI values at baseline were associated with an increased risk of fractures, reinforcing the importance of CGA in predicting fractures in older people. 

We included CLSA participants who completed the baseline (2015) comprehensive interview and had dualenergy X-ray absorptiometry (DXA) (N = 28,781). We describe the age-and sex-stratified proportion and prevalence of people at high fracture risk (FRAX® major osteoporotic fracture probability > 20%) and not taking an osteoporosis medication. Osteoporosis medications were defined using the Public Health Agency of Canada standards for osteoporosis surveillance and identified via drug identification numbers. 2 Sampling weights, as defined by the CLSA, were applied. 1 Results: The mean age of participants was 70.0 (SD 10.3). Overall, 6.2% were at high fracture risk. Of people who were at high risk, 96.6% of men and 79.8% of women were not taking an osteoporosis medication. This proportion decreased with age, for both men ( assess patients' preference to adopt lifestyle changes to prevent osteoporotic fractures. Methods: A discrete-choice experiment was conducted in seven European countries: Belgium, France, Ireland, Spain, Switzerland, the Netherlands and United Kingdom. Patients were repetitively asked if they would closely follow different regimens of lifestyle recommendations that varied with respect to 6 attributes and different levels (options): physical activity (levels: not included, moderate or high), calcium and vitamin D status (levels: not included, taking supplements or improve nutrition and assure a minimal daily sunlight exposure), smoking (levels: not included or quit smoking), alcohol (levels: not included or moderate consumption), weight reduction (levels: not included or ensure a healthy body weight) and fall prevention (levels: not included, receive general advice or following a one-day prevention program). A conditional logit model was used to estimate patient's preferences for all participants (global model) and per country. Results: In total, 1042 patients completed the questionnaire, with samples varying between 91 and 244 per country. Overall, patients were favourable to lifestyle changes for preventing osteoporotic fractures (positive and significant coefficients in the global model as well as in all countries separately). However, among the lifestyle factors proposed, consensually across all countries, patients were not prone to engage in high physical activity (i.e. walking for 30-40 minutes, 3-4 times per week or equivalent). In Ireland, Belgium, the Netherlands and Switzerland, patients were not favourable neither to follow a one-day falls prevention program. Belgian, Swiss and Dutch patients were not prone neither to modify their nutrition (i.e. diet rich in calcium and consumption of fish at least twice a week) and ensure a 10-15 minutes daily sunlight exposure. In the global model as well as for Belgian and Dutch patients separately, we observed favourable intention from patients to reduce their alcohol consumption, engage in moderate physical activity, taking calcium and vitamin D supplements and ensure a normal body weight for preventing fractures. Conclusions: Patient's healthy lifestyle behaviours are essential for an optimal osteoporosis management. This is the first study that explicit patients' preferences for lifestyle factors in preventing osteoporotic fracture. In an ideal patient-centred approach, fracture prevention should take these considerations and preferences into account.

Background: Previous studies have shown that patients with primary hyperparathyroidism (PHPT) have an increased risk of fractures and other comorbidities such as cardiovascular events, but the effect of parathyroidectomy (PTX) on these outcomes, has been insufficiently studied. Most previous studies have been limited in size and results have not been consistent. Method: In this retrospective cohort study of all patients diagnosed with PHPT (ICD-10 E210) at hospitals in Sweden between July 1 st 2006 and Dec 31 st 2017, we investigated the association between PHPT diagnosis, parathyroidectomy, and outcomes. In total, we identified 16 652 patients with PHPT who were assigned 166 520 age and sexmatched controls from the general population. The primary aim of this study was to investigate whether the diagnosis of PHPT was associated with an increased risk of fractures and cardiovascular events (CVE). The secondary aim was to determine if PTX in patients with PHPT diagnosis was associated with a reduced risk of these outcomes. Results: The majority of the patients were female (78.2 %), the mean (standard deviation) age 67.4 (12.8) years, and the follow-up time for the entire patient group was 35 423 patient-years. In a Cox proportional hazards model, adjusted for age, sex, and calendar year, patients with PHPT had a higher risk of any fracture (adjusted HR 95% CI: 1.30 (1.22-1.38)), hip fracture (1.25 (1.11-1.40)), and major osteoporotic fracture (1.28 (1.19-1.38)) compared to controls. Furthermore, patients with PHPT had a higher risk of cardiovascular events (1.46 (1.35-1.57)) and death (1.44 (1.37-1.52)). In a Poisson regression model with PTX as a time-dependent variable, PTX was associated with reduced risk of hip fracture (HR 0.77 (0.61-0.97), any fracture (HR 0.83 (0.74, 0.92)) and CVE (HR 0.77 (0.68-0.88) in patients with PHPT. Conclusions: Patients with primary hyperparathyroidism have an increased risk for fractures, cardiovascular events, and death. Parathyroidectomy was associated with a reduced risk of fractures and cardiovascular events, indicating that surgery could have beneficial effects in patients with PHPT. Objective: Frailty represents a huge public health burden. Fundamental aging processes (e.g. chronic inflammation) are associated with frailty, but the independence of these relationships from age, sex, lifestyle and adiposity is unclear. Using UK Biobank, we investigated associations between frailty, blood biomarkers and bone health, independent of these characteristics. Material and Methods: 502,640 participants aged 40-69 years were recruited to UK Biobank 2006-10. Venous blood samples were obtained. From 2014 onwards, a subset attended an imaging follow-up, including whole-body DXA (GE Lunar iDXA), grip strength (Jamar dynamometer), and a questionnaire. Frailty was defined using a modification of Fried's classification (at least 3 of weight loss, mental exhaustion, low physical activity, slow gait speed and low grip strength). The presence of 1-2 criteria designated pre-frailty. Linear regression was used to discern associations between frailty status, biochemical markers (CRP, 25(OH)-vitamin D, HbA1c) and bone outcomes, adjusting for age, sex, smoking, alcohol, educational level and total fat mass assessed by DXA. Non-frail was the reference category and blood biomarkers were standardised (β: mean difference in SD). Results: 22,332 participants (11,484 women, 10,848 men) with frailty assessment and DXA bone measures or blood biochemistry were included in the analysis; 547(2.4%) were frail and 9359(41.9%) pre-frail. Frail participants were more likely to be female [59.6% vs. 50.9%], older [mean(SD) 63.2(7.9) vs. 62.6(7.3)years], of higher BMI [mean(SD) 30.7(6.4) vs. 25.9(4.0)kg/m 2 ]. After full adjustment, frail participants had higher CRP [+0.34 SD(95% CI 0.18, 0.51], lower 25(OH)-vitamin D [-0.36 SD(-0.54,-0.19)] and higher HbA1c [+0.27 SD(0.10, 0.43)], all p<0.001. Frail participants had lower femoral neck [-0.03 g/cm 2 (-0.05, -0.01),p=0.02] and lumbar spine bone mineral density (BMD) [-0.03 g/cm 2 (-0.05, -0.002),p=0.002]. BMD associations were only apparent after fat adjustment. Similar associations were observed for pre-frail vs. non-frail participants. Conclusion: In UK Biobank, frailty is associated with high levels of systemic inflammation, low 25(OH)-vitamin D, poorer glucose handling and lower BMD, independent of age, sex, lifestyle and fat mass. These findings suggest that frailty associations with age-associated inflammation (inflammaging) are only partly mediated via adiposity and warrant further mechanistic investigation. Objectives: Epigenetic clocks are composed of a selection of CpG sites which have the potential to capture 'biological age' and provide a measure of age acceleration (calculated as the difference between biological and chronological age). Here we investigate the associations between age acceleration (according to three different clocks: Horvath pan-tissue, GrimAge and PhenoAge) and hip DXA parameters. Materials and methods: Participants were recruited across three generations of the Hertfordshire Intergenerational Study; original cohort members, their children, and grandchildren. Hip DXA was performed (Lunar iDXA, GE Healthcare) and whole blood DNA methylation was analysed using the Illumina 850k array (Infinium MethylationEPIC BeadChip) following which GrimAge, PhenoAge and Horvath pantissue age acceleration were calculated. Associations with DXA hip measures (including Bone Mineral Density (BMD), Bone Mineral Content (BMC) and bone area) were analysed using linear regression in sex-stratified unadjusted models and those adjusted for age and BMI. Results are presented as β coefficients with 95% confidence intervals. Results: A total of 114 participants (39 males and 75 females) were recruited, mean age of 56 years (range 18 to 88). Relationships varied in different clocks; Horvath pan-tissue age acceleration was not associated with DXA measures in any models. However, greater GrimAge acceleration was associated with significantly lower hip BMC (β=-0.94 (-1.50,-0.38), p<0.01 and lower bone area (β= -0.28 (-0.55,-0.01), p<0.05) in males in fully-adjusted models, and with lower hip BMD in males in unadjusted models (β= -0.02 (-0.04,-0.01), p<0.05). Greater PhenoAge acceleration was associated with lower hip BMC in males in models adjusted for age and BMI (β= -0.34 (-0.65,-0.03), p<0.05) and lower hip BMD in males in unadjusted models only (β= -0.01 (-0.02,-0.00), p<0.05). No significant associations were observed in females.

Our results demonstrate that the newer iterations of epigenetic clocks (GrimAge and PhenoAge) which were designed to measure age-related phenotypic changes are associated with bone measures at the hip, whereas the first-generation clocks (Horvath pan-tissue) were not. These sex-specific associations require further investigation.

F. Thomasius 1 , S. Palacios 2 , A. Alam 3 , M. Boolell 3 , F. Vekeman 4 , G. Gauthier 4

Objective: This study aimed at comparing the risk of fractures and economic outcomes between women with osteoporosis receiving risedronate GR vs alendronate immediate-release. Risedronate GR offers a more convenient dosing option by eliminating the need for fasting and has a higher oral bioavailability ‡ than alendronate. Material and Methods: Women with osteoporosis from a US claims database (2009-2019) were analyzed. They were observed for ≥2 years following the date of their first observed dispensing for an oral bisphosphonate and classified into the GR or alendronate cohort based on the treatment initiated on that date (index date). Women from the two cohorts were then matched 1:1 based on demographic and clinical characteristics evaluated during a six-month period prior to the index date. Incidence rates (IRs) of fractures and healthcare resource utilization per 1,000 patient-years were compared between the two cohorts using IR ratios (IRRs (Copley, 12; Confirm, 14) . Copley evaluated the AGN1 implant resorption and replacement with bone utilizing sequential radiographs and computerized tomography (CT) scans at 12 wks, 24 wks and 5-7 years. The Confirm study is ongoing and will collect follow-up data to 5 years. Results: Subjects were aged 70 ± 10 with a baseline mean femoral neck T-Score of -3.0 ± 0.5 (N = 26). The mean pre-operative FRAX score for 10-year probability of hip fracture was 11 ± 10% (N = 26). Skinto-skin surgical time was 16 ± 4 min (N = 14). The mean volume of injection was 17.6 ± 2.6 cc (N = 26). CT and radiographs demonstrated complete AGN1 resorption and replacement with bone (N = 26). Baseline femoral neck BMD was not statistically different between studies (p = 0.085). After 2.1 ± 0.4 years, the mean percent difference in BMD increased by 61% ± 37% (p < 0.001) from baseline (N = 26). All patients were weight bearing as tolerated after surgery and returned to activities of daily living in less than one week. Conclusion: This data supports the use of AGN1 LOEP for high-risk patients with osteoporosis-related bone loss and demonstrates that the treatment significantly improves BMD from baseline which is expected to reduce hip fracture risk. The overall impact of LOEP on hip fracture reduction is currently being evaluated in an ongoing multi-national randomized, controlled, prospective, single-blinded clinical study. 

In this multicenter prospective observational post-authorisation safety study conducted in Italy and Spain, post-menopausal women (PMW) with osteoporosis (naïve to bisphosphonates (BP)) were treated weekly with ALN-EFF and followed for 12 ± 3 months. Information was collected on AEs, MEs (error in following administration instructions), persistence and compliance. Results: Patients (N = 1,028) aged 67 ± 9 years (mean ± SD) received ALN-EFF weekly. The cumulative incidence of upper GI AEs related to ALN-EFF (primary endpoint) was 9.6%, vast majority being of mild intensity. The most frequently occurring upper GI AEs related to ALN-EFF were dyspepsia (2.7%), gastroesophageal reflux disease (2.4%), and nausea (2.2%). None of the relevant upper GI AEs listed in the primary endpoint and no serious AEs were reported. At least one ME occurred in 29.9% of patients. However, the majority of MEs were associated with administration instructions applicable to any oral BP and only 7 MEs were associated with ALN-EFF. Some studies have highlighted the relationships between muscle health and structural changes in brain, while the relationships with functional changes in brain has never been fully explored. In this study, we aimed thus to investigate functional brain processes in dynapenia.

Methods: This single-centre, cross-sectional study included 62 community-dwelling older adults (mean age 73.1 years; 59 females) in Geneva (Switzerland). Participants underwent i) detailed skeletal muscle assessments as well as ii) functional magnetic resonance imaging (fMRI) acquired on a 3 Tesla MRI scanner (Siemens® Trio, Germany) during the performance of a dual-task paradigm, consisting of a visual baseline, two single-tasks (motor joystick and arithmetic task) and a dual-task (motor and arithmetic task combined). Low muscle strength was defined according to handgrip strength (JAMAR® dynamometer) and/or chair rise time measurements using the EWGSOP2 cut-off points. Results: 47% (29/62) of participants were classified as dynapenic according to EWGSOP2. No differences were found between dynapenic and non dynapenic groups in regard to cognitive (MMSE) and frontal executive functioning (FAB), and gait speed. fMRI results reveal a differential recruitment of motor circuits in the brain during the dual-task condition in dynapenic as compared with non dynapenic participants. In particular, while the brain activity during the single-tasks did not differ between the two groups, only during the dual-task condition non dynapenic participants showed significant increased activation in the premotor cortex as compared to dynapenic participants. This could be interpreted such that in dynapenia there is an insufficient recruitment of activity in the brain's motor areas, when a task gets more complex.

Our results point to a dysfunctional involvement of brain activity in dynapenia in a multi-tasking paradigm. A better knowledge of the link between dynapenia and brain functions could provide new impulses in the diagnosis and development of effective early-targeted interventions for sarcopenia. There were three main study components: 1) latent class analyses (LCA) to identify distinct care pathways ("classes") that were statistically and clinically meaningful, representing common patterns of health service use in patients over 12-months; 2) multivariable logistic regression to analyze associations between each class and HRQoL recovery; and 3) a micro-costing analysis to determine direct health care costs per participant in each class (2020 Australian Dollars) and post-hoc Bonferroni tests to determine significant differences.

The LCA determined 20 classes across the four fracture sites. Different classes were associated with HRQoL recovery at 12-months, although theses classes generally included the combination of primary care; allied healthcare; osteoporosis medication use; vitamin D/calcium supplementation; and non-opioid analgesic use. The total direct cost of fractures was estimated at $89,564, $38,926, $18,333, and $39,461 per patient for hip, vertebral, wrist and humeral participants, respectively. The cost analysis identified that classes associated with HRQoL recovery were also less costly. Conclusions: By using LCA on health service use, we were able to identify several multidisciplinary care pathways for individual fracture sites and determine the cost and impact of each care pathway on HRQoL recovery. These care pathways may assist health care providers worldwide in allocating resources for fractures in more cost-effective ways. Objective: Joint discomfort is a common issue seen in athletes and in normal active people. UC-II® undenatured type II collagen is a dietary ingredient derived from chicken sternum and has been shown in clinical studies to support knee joint comfort and flexibility. Herein, we report results from a 24 week randomized, placebo-controlled, double-blind study evaluating the efficacy and tolerability of UC-II® collagen in managing knee joint discomfort and mobility in healthy subjects who experience activity-related joint pain. Material and Methods: Healthy subjects, (n = 96), who reported knee joint pain of 5 on an 11-point Likert scale while performing a single-leg-step-down (SLSD) test were randomized to receive placebo (PLA, n = 48), or 40 mg/day of UC-II® providing ≥ 3% undenatured type II collagen (n = 48) for 24 weeks. Joint mobility was measured from the daily number of steps using a step counter (without sporting activity). While joint discomfort was evaluated using subjective questionnaire including the Knee Injury and Outcome Score (KOOS). Results: At the end of the study, subjects in collagen group reported taking higher number of daily steps than baseline value. A sub groupanalysis based on gender showed significantly higher number of daily steps in males from the collagen group versus the PLA group (+ 669 steps vs. -526 steps, p = 0.0374). Similarly, a subgroup analysis based on age showed that collagen supplemented subjects between 20 and 35 years old took higher numbers of steps on SLSD test before reporting the pain score of 5 on the Likert scale, and this change was significant versus the pre-supplementation value (p = 0.0409). In terms of joint discomfort measures, collagen group reported a significant decrease in the duration of knee pain during regular sporting activities versus the PLA group (p < 0.05). Furthermore, the analysis of KOOS subscale data demonstrated a significant reduction in joint discomfort during sports or recreational activities in collagen group versus the baseline value (p = 0.0009) and no significance observed between the treatments. Collagen supplemented group also showed improved quality of life over the study period (p < 0.05). No significant change was observed in the PLA group. As for the KOOS individual questions, collagen group experienced significant reduction in knee pain versus the PLA group during knee twisting/pivoting (p = 0.0346), while walking descending stairs (p = 0.0215) and walking on a flat surface (p = 0.0241) after 24 weeks of supplementation.

In conclusion, these results suggest that UC-II® undenatured type II collagen supplementation supports joint mobility and may reduce joint discomfort during the activities of daily living.

The prevalence of radiographic hip OA was 18.4% and 14.4% in men and women, respectively in the baseline survey and 16.0% and 10.7%, respectively in the 4 th survey. The prevalence of radiographic hip OA in men and women aged 40-60 years was significantly lower in the 4th survey than in the baseline survey and was significantly lower only in men in their 70 s in the baseline than in the 4th survey. Logistic regression analysis performed after adjustment for age, sex, body mass index, and communities showed that the prevalence of radiographic hip OA in the 4 th survey was significantly lower than that in the baseline survey (odds ratio 0.55, 95% confidence interval 0.46-0.65).

In the population-based survey with a 10-year interval, the prevalence of radiographic hip OA tended to decrease. This preferable change in radiographic hip OA circumstances could contribute to the decrease in the occurrence of osteoporotic fracture in the future. Background: Knee osteoarthritis (OA) is a painful condition frequently treated by intra-articular (IA) corticosteroid injections. Lorecivivint (LOR), a novel IA CLK/DYRK inhibitor that modulates Wnt and inflammatory pathways, is in development as a potential knee OA treatment. While LOR is proposed for stand-alone use, in clinical practice, providers might administer LOR in close time proximity to IA corticosteroid. This open-label, parallel-arm, healthy volunteer study was conducted to assess safety, tolerability, and pharmacokinetic interactions between LOR and triamcinolone acetonide (TCA) when the two medications were administered 7 days apart. Methods: Healthy volunteers were randomized 1:1 to Treatment Arm 1 (IA 40 mg TCA on Day 1 followed by IA 0.07 mg LOR on Day 8) or Treatment Arm 2 (IA 0.07 mg LOR on Day 1 followed by IA 40 mg TCA on Day 8). All injections were performed on the right knee. For each treatment arm, treatment-emergent adverse events (TEAEs) were categorized by "epoch", with Epoch 1 spanning from first until second injection, and Epoch 2 spanning from second injection until end of study. In Treatment Arm 1, plasma TCA levels were assessed on Days 1 (before TCA dosing and up to 12 h after), 2 (24 h after), 3, 5, 8 (before LOR dosing and up to 8 h after), 11, and 15. Plasma LOR concentrations were assessed on Day 8 (before LOR dosing and up to 8 h after). In Treatment Arm 2, plasma LOR levels were assessed on Days 1 (before LOR dosing and up to 8 h after), 8 (up to 8 h after TCA dosing), 9 (24 h after), 10, and 12. Plasma TCA levels were assessed on Days 8 (before TCA dosing and up to 12 h after), 9 (24 h after), 10, 12, 15, 18, and 22. Results: Forty subjects (age 41.3 ± 7.2 years; BMI 27.8 ± 2.98 kg/m 2 ; female 40.0%) were evaluated. A total of 18 TEAEs were reported by 11 (27.5%) subjects (Table 1) . LOR injection-related TEAEs were similar between arms and there were no serious adverse events. In all subjects and at all time points, plasma LOR concentrations were below the limit of quantification (0.1 ng/ml). Geometric mean concentrations and PK parameters for TCA were similar between treatment arms (Fig. 1) . Conclusion: There were no quantifiable plasma concentrations of LOR in either treatment arm, and the PK of TCA was not changed when administered after LOR injection compared to when administered alone. No safety signals were observed. These results suggested administering LOR and TCA within a 7-day period of each other should not pose a safety concern.

D levels were 82.7 ± 27.5 ng/mL (HyD), 55.4 ± 8.5 ng/mL (VD 3 ), 33.1 ± 14.4 ng/mL (placebo), ANOVA P < 0.001. After adjustments for baseline 25OHD and BMI, the mean (SE) percent change in total (type I/II) FCSA was -4.3 ± 9.2% (HyD), 25.1 ± 9.1% (VD 3 ), 4.7 ± 8.4% (placebo), with P = 0.033 between HyD and VD 3 . More pronounced differences between HyD and VD 3 were noted in type I compared to the type II fibers. Percent changes in VDR and PAX-7 concentrations did not differ significantly by group (all P > 0.223). Conclusion: Although HyD vs. VD 3 resulted in higher final 25OHD levels, muscle fiber size significantly increased with VD 3 and did not change with HyD in 6 months in younger postmenopausal women. This result supports concerns that higher 25OHD levels may not benefit skeletal muscle outcomes. This study was supported by DSM Nutritional Products, Inc. Backgrounds: Recently, several papers have made the hypothesis that sarcopenia might partially due to a nervous system failure. Indeed, part of the diagnosis is based on volitional tasks that require the integrity of the nervous system to be properly realized. In the recent years, neurofilament light chains (NF-L) have emerged as a new highly specific blood-biomarker of neuronal damage. Its expression has been reported to be modified in both central and peripheral neuropathies as well as traumatic brain injuries. Objectives: In this study, we measured NF-L in a large cohort of older individuals to define its expression in presence of sarcopenia.

The SarcoPhAge cohort is a Belgien cohort of communitydwelling older adults. A diagnosis of sarcopenia was established according to the European Working Group on Sarcopenia in older People 2 (EWGSOP2) criteria. Muscle strength was evaluated with a hydraulic hand-dynamometer, appendicular lean mass by Dual-Energy X-Ray Absorptiometry and physical performance by the Short Physical Performance Battery test (SPPB). NF-L, was measured on all the available sera collected at time of inclusion (n = 409) using the SiMoA technology (Quanterix°). Results: NF-L was increased in sarcopenic patients (median NF-L: 43.0 pg/mL) compared to controls (median NF-L: 21.1 pg/mL) (p-value: < 0.0001). We also observed a significant difference between subjects with high SPPB score (score: 10 -12) (median NF-L: 19.5 pg/ mL), intermediate SPPB score (score: 7 -9) (median NF-L: 24.5 pg/ mL) and low SPPB score (score: 0-6) (median NF-L: 27.7 pg/mL) (p-value: < 0.0001). The rank correlation gave a Spearman's rho of -0.267 (p-value < 0.0001). A significant correlation was also observed between appendicular lean mass/height 2 (ALM/h 2 ) and NF-L (rho: -0.200; p-value < 0.0001) but also between handgrip strength and NF-L (rho: -0.196; p-value = 0.0001). In a multiple regression after adjustment for potential confounding variables, NF-L was independently associated with SPPB score (p-value: < 0.0001) but not with ALM/h 2 or handgrip strength.

In this study, we showed that NF-L is increased in sarcopenic patients and is more particularly associated with SPPB score.

Our results suggest that sarcopenia may share common features with neurodegeneration. Introduction: Bone mass is known to decline in aging men and this decline is in part affected by sex steroid exposure. However, it is unclear how early after achieving peak bone mass bone loss begins and whether this decline is associated with sex steroid levels in young adulthood.

Objective: Investigating longitudinal changes in trabecular and cortical vBMD in relation to sex steroid levels, body composition and lifestyle factors in young adult men. Methods: Longitudinal observational study. 999 healthy men aged 24-46 years of whom 691 were re-evaluated after a mean period of 12 years. Serum sex hormone binding globulin (SHBG) levels were measured using immuno-assay. Testosterone (T), estradiol (E2), were measured using LC-MS/MS, free T calculated (cFT). Volumetric BMD was determined at the non-dominant arm (radius, at 4% and 66% of bone length from distal) using pQCT (Stratec XCT-2000, Stratec Medizintechnik, Germany, version 6.0). Linear mixed models were used for statistical analyses. All models comprised lifestyle factors and were adjusted for age and body mass index (BMI). A major use of FRAX has been its incorporation into treatment and assessment guidelines. The setting of intervention thresholds (the fracture probability above which to recommend treatment) has varied in different countries. Guidelines variously use an age-dependent fracture probability, or a fixed probability threshold applied to all relevant ages. In the UK, the National Osteoporosis Guideline Group (NOGG) have adopted a hybrid threshold. For men and women, the intervention threshold up to age 70 years is set at a risk equivalent to that associated with a prior fracture and therefore rises with age. At age 70 years and above, fixed thresholds are applied. The proportion of women potentially eligible for treatment rises from approximately 30% to 50% with age, largely driven by the prevalence of prior fracture.

The development of new anabolic interventions for osteoporosis has widened the strategies for its management, in particular, the need to identify patients at very high risk. Such patients might be preferentially targeted with an anabolic agent in the first instance, followed by an inhibitor of bone resorption to maintain a long-term response. NOGG has developed thresholds that characterise men and women with high and very high fracture risk; very high risk is classified as a fracture probability that exceeds the original (and current) intervention threshold by 60%. The proportion of women at very high risk rises from approximately 7% to 36% with age. Clinical scenarios that determine very high risk commonly arise through a combination of clinical risk factors. Additionally, a recent fracture within the past two years has been shown to increase the risk of refracture over and above that calculated by FRAX. Adjustments to FRAX probabilities have been made available to account for the recency of fracture. Such adjustments identify very high risk patients, particularly those with a recent vertebral fracture.

Objectives: MicroRNAs (miRNAs) demonstrated to be key regulators of bone modelling and remodelling, through epigenetic post-transcriptional control of gene expression in bone cells. Deregulation of expression and/or activity of specific miRNAs may concur to osteoporosis development and fragility fracture risk. Serum dosage of specific circulating microRNAs (c-miRNA) has recently become subject of investigation by the scientific community as possible early-stage and non-invasive diagnostic biomarkers for osteoporosis and/or prognostic marker for the individual risk of osteoporosis-associated fragility fractures.

The expression of human miRNAs was measured, by next generation sequencing (NGS), in serum samples of 50 osteoporotic patients (18 without fracture, 18 with lumbar spine fracture and 14 with femoral neck fracture) vs 30 individuals with normal bone mass (T-score at lumbar spine, femoral neck and total femur ≥ 1), who have not received any anti-fracture medical therapy at the time of serum collection. c-miRNAs, identified as significantly differentially expressed between the two groups, were validated by Droplet-Digital-PCR (ddPCR) technology in a larger number of serum samples, from untreated patients, presenting different bone phenotypes [105 with osteoporosis (54 without fracture, 32 with lumbar spine fracture, 16 with femoral neck fracture and 3 with both spine and femur fracture), 62 with osteopenia and 46 with healthy BMD. Results: NGS identified 5 miRNAs (miR-8085, miR-320a-3p, miR-23a-3p, miR-4497, miR-145-5p) as differentially expressed between non-fractured osteoporosis cases and normal bone samples. ddPCR confirmed miR-23a-3p as less expressed in osteoporosis, with or without fracture, than osteopenia and normal bone, miR-320a-3p as more expressed in osteoporosis with fracture and less expressed in osteoporosis without fracture, both with respect to the other two groups of bone phenotypes, and identified miR21-5p as more expressed in osteoporosis, with or without fracture, than osteopenia and normal bone. Conclusions: Our data suggested these three c-miRNAs as possible serum diagnostic biomarkers of osteoporosis. Circulating miR-320a-3p appeared to be a promising prognostic indicator of fracture risk in osteoporotic patients. Further studies, in larger and different populations, are needed to confirm these data, to translate the use of c-miRNAs as diagnostic and prognostic biomarkers of osteoporosis and fracture into the clinical practice.

NHS: N = 76). Mean [SE] new HO was 57.0% lower with PVO

most common treatment-emergent AEs were mucocutaneous: dry skin (67.4%), lip dryness (44.2%), alopecia (34.9%)

Conclusion(s): PVO may be an important therapeutic option in FOP

Acknowledgements: This study was sponsored by Ipsen. Disclosures: RJP: Research investigator: Clementia/Ipsen, Regeneron; Advisory board: President of the International Clinical Council on FOP; MAM: Research support: Clementia/Ipsen, Regeneron

AMC: Research investigator: Clementia/Ipsen, Regeneron; Consultant: Ipsen; CDC: Research investigator: Clementia/Ipsen; Speaker: Biogen; PD: Research investigator: Clementia/Ipsen. Member of the International Clinical Council on FOP; ECH: Principal investigator at UCSF for all palovarotene clinical trials in FOP; sub-investigator for clinical trials of palovarotene in MO, and for a clinical trial sponsored by Neurocrine Biosciences, Inc.; member of the International Clinical Council on FOP, Fibrous Dysplasia Foundation, and IFOPA Registry advisory board (all voluntary); PK: Research investigator: Clementia/Ipsen; RK: Research investigator: Clementia/ Ipsen, Kyowa Kirin, Regeneron; Advisory board: IFOPA FOP Registry Medical Advisory Board

FSK: Research investigator: Clementia/Ipsen, Regeneron; Advisory Board: IFOPA Medical Advisory Board; Founder and Immediate Past

Acknowledgements: Pharmaceutical industries and donors support Acknowledgements None. Disclosures AP received funding from Amgen. Acknowledgments: This study is funded by the Swiss National Science Foundation (grant #32003B_166690) and FROMO Foundation. Acknowledgments: We are grateful to participants for their participation in the study. Lonza CHI Inc., Morristown to support the study. Disclosures: Vijaya Juturu, Shane Durkee and Zainulabedin Saiyed are Lonza CHI Inc. Employers.

Objectives: NSAIDs are commonly used in the setting of musculoskeletal disorders. It has been hypothesized that NSAIDs might have weak but beneficial effects on bone health, including fracture risk, but most studies have been unable to adjust for potential confounders. We explored the relationship between NSAIDs and fracture risk within the setting of a well-documented, randomised, placebo-controlled study of the bisphosphonate, clodronate. Material and Methods: 5212 community-dwelling, women age 75 years and older, unselected for osteoporosis were included in this single centre trial. Clodronate 1600 mg daily was compared to placebo over a 3 year treatment period, and reduced osteoporotic fracture risk by 23%. Concurrent medication use at baseline was used to identify those prescribed oral NSAIDs. Only verified, incident fractures were included in the analysis. Using Cox regression, the impact of NSAIDs on fracture risk was examined as well as the anti-fracture efficacy of clodronate in those using or not using NSAIDs. Results: 1082 (20.8%) women reported use of NSAIDs at baseline. They were slightly, but significantly, younger (mean 79 vs 80 years, p = 0.004) and heavier (mean 66.7 vs 64.7 kg, p < 0.001) than nonusers, with slightly higher femoral neck BMD (FN-BMD, 0.66 vs 0.64 g/cm2, p < 0.001). When adjusted for age, FN-BMD and weight, NSAID use was associated with a significant increase in osteoporotic fracture risk (HR 1.29, 95%CI 1.03-1.62, p = 0.025). However, this increase in risk was not statistically significant in the placebo group (HR 1.14, 0.84-1.55). In women receiving clodronate, the effect of the bisphosphonate to reduce osteoporotic fracture risk was not observed in those receiving NSAIDS (HR 0.95, 0.65-1.41, p = 0.81) in contrast to those not using NSAIDs (HR 0.71, 95%CI 0.58-0.89, p = 0.002). Conclusion: The analysis suggests that the efficacy of the bisphosphonate, clodronate, to reduce fracture risk was negated in those receiving NSAIDs. The mechanism, if real, is unclear, but this observation may be of significant clinical importance. Further exploration in other studies with commonly used oral bisphosphonates is required.